title: Establishment of an index with increased sensitivity for assessing murine arthritis.
abstract: The goals of our study were to establish quantitative outcomes for assessing murine knee arthritis and develop an Arthritis Index that incorporates multiple outcomes into a single calculation that provides enhanced sensitivity. Using an accepted model of meniscal/ligamentous injury (MLI)-induced osteoarthritis (OA), we assessed mouse knee arthritis using several approaches. Histology-based methods were performed to visualize joint tissues including articular cartilage and subchondral bone. Accepted histologic scoring methods and histomorphometry were performed to grade cartilage degeneration and determine articular cartilage area, respectively. MicroCT was used to visualize and quantify the bony structures of the joint including osteophytes and joint bone volume. A statistical algorithm was then developed that combined histologic scores and cartilage areas into a single Arthritis Index. MLI induced progressive, OA-like articular cartilage degeneration characterized by increasing (worsening) histologic score and decreasing cartilage area. MicroCT revealed osteophytes and increased joint bone volume between the femoral and tibial physes following MLI. Lastly, an Arthritis Index calculation was established, which incorporated histologic scoring and cartilage area. The Arthritis Index provided enhanced quantitative sensitivity in assessing the level of joint degeneration compared to either histologic scoring or cartilage area determination alone; when using the Index, between 29% and 43% fewer samples are needed to establish statistical significance in studies of murine arthritis. Arthritis in the mouse knee can be quantitatively assessed by histologic scoring, measuring cartilage area, and determining joint bone volume. Enhanced sensitivity can be achieved by performing the Arthritis Index calculation, a novel method for quantitatively assessing mouse knee arthritis.
authors.affiliation: Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York 14642, USA. erik_sampson@urmc.rochester.edu
authors.forename: Erik R
authors.initials: ER
authors.lastname: Sampson
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Beck
authors.forename: John
authors.initials: J
authors.lastname: Ketz
authors.forename: Krista L
authors.initials: KL
authors.lastname: Canary
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hilton
authors.forename: Hani
authors.initials: H
authors.lastname: Awad
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: Regis J
authors.initials: RJ
authors.lastname: O'Keefe
authors.forename: Randy N
authors.initials: RN
authors.lastname: Rosier
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zuscik
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000473:pathology*; D012720:Severity of Illness Index